RESUMO
Glycyrol (GC) is one natural active product. Imiquimod-induced psoriasis-like Balb/c mouse models were established. The model mice were intraperitoneally injected with cyclosporine A (CsA) and GC for 8 days followed by a series of biological detections. GC had little toxicity according to the levels of peripheral blood cells, hemoglobin, blood urea nitrogen (BUN), and serum creatinine (CRE), while CsA significantly increased the levels of BUN and CRE. GC decreased the splenic index and reduced the expressions of IL-6, IL-23, and CXCL-3 in the model mice and IL-6, CXCL-1, and CXCL-2 in the inflammatory HaCaT cells. The half inhibition concentration (IC50) of GC on HaCaT cells was 29.72 µmol/L, resulting in improved apoptosis, enhanced expressions of p21, BAX, and BIK, and reduced expressions of BCL-2. GC is an immunosuppressive agent against psoriasis-like symptoms by anti-inflammatory effects, which provides a strategy for the discovery of anti-psoriatic natural products.
Assuntos
Dermatite , Psoríase , Camundongos , Animais , Interleucina-6/metabolismo , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Dermatite/metabolismo , Anti-Inflamatórios/efeitos adversos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Imunossupressores/efeitos adversos , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças , Pele/metabolismo , Citocinas/metabolismoRESUMO
BACKGROUND: Opioid prescription for inflammatory bowel disease (IBD)-related pain is on the rise. However, the use of strong opioids can result in severe complications, and even death, in IBD patients. This study aimed to define the role of fentanyl and morphine, two representative strong opioids, in the pathogenesis of dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis. METHOD: DSS and TNBS models were induced in C57BL/6J and Balb/c mice, respectively. Disease activity index (DAI), histopathology, enzyme-linked immunosorbent assay (ELISA), multiplex ELISA, and flow cytometry were performed to evaluate the effects of fentanyl and morphine. RESULT: Fentanyl exacerbated DSS- and TNBS-induced colitis, while morphine exhibited no significant immunomodulatory effect. Fentanyl and morphine had no obvious effects on the serum levels of adrenocorticotropic hormone (ACTH), glucocorticoid (GC), and prostaglandin E2 (PGE-2) in DSS and TNBS models. Fentanyl elevated the proportions of Th1 cells, µ-opioid receptor (MOR) + Th1 cells, and MOR + macrophages in the colonic mucosa of DSS-treated mice, and enhanced the proportions of Th1 cells, macrophages, MOR + Th1 cells, and MOR + macrophages in the colonic mucosa of TNBS-treated mice. We found that fentanyl upregulated the levels of inflammatory cytokines/chemokines in MOR + macrophages of the colonic lamina propria mononuclear cells (LPMCs) from DSS-treated mice, whereas it had no effect on the expression of most inflammatory cytokines/chemokines in MOR + macrophages in the colonic LPMCs from TNBS-treated mice. CONCLUSION: Our findings suggest that fentanyl exacerbates murine colitis via Th1 cell- and macrophage-mediated mechanisms, while morphine exhibits no significant immunomodulatory effect.
Assuntos
Fentanila , Morfina , Camundongos , Animais , Ácido Trinitrobenzenossulfônico/toxicidade , Fentanila/farmacologia , Camundongos Endogâmicos C57BL , Morfina/farmacologiaRESUMO
Mesenchymal stem cells (MSCs) have been proved to exert anti-inflammatory effects and regulate immune reactions. Traditional Chinese medicine (TCM), qi-fang-bi-min-tang, is effective for some patients with allergic diseases. However, it remains unclear whether MSCs combined with TCM could benefit the treatment of allergic rhinitis (AR). In this study, we reported an additional effect of TCM (qi-fang-bi-min-tang) on the therapy of AR under MSCs treatment. Intriguingly, we observed that TCM-treated MSCs significantly inhibited the symptoms of AR and reduced the pathological changes of nasal mucosa in ovalbumin (OVA)-induced rats. The expression levels of interferon γ (IFN-γ), interleukin-17 (IL-17), and IL-4 were significantly decreased in the plasma of AR rats after injection of TCM-treated MSCs. TCM-treated MSCs reduced the levels of histamine secreted by mast cells and immunoglobulin E (IgE) secreted by plasma cells. In addition, we found that MSCs combined with TCM had a better therapeutic effect than TCM alone on AR in an OVA-induced mouse model. After OVA induction, MSCs combined with TCM significantly reduced the ratio of T helper type 1 (Th1), Th2, and Th17, but increased the proportion of Treg in the spleen of mice. Consistently, the expression levels of IFN-γ, IL-4, and IL-17 were significantly decreased, but transforming growth factor-ß1 was significantly increased in the plasma of AR mice after treated with TCM and MSCs. Our results from both rats and mice indicated that the effects of TCM combined with MSCs on the AR might be through regulating the secretion of Th1, Th2, and Th17 cytokines. This study suggested that TCM (qi-fang-bi-min-tang)-treated MSCs could be used in the clinical therapy of AR.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Rinite Alérgica/terapia , Aloenxertos , Animais , Citocinas/imunologia , Masculino , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-Dawley , Rinite Alérgica/imunologia , Rinite Alérgica/patologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/patologiaRESUMO
Rheumatoid arthritis (RA) is an autoimmune disease associated with synovial hyperplasia and bone and cartilage destruction. T cells, notably T helper (Th)-1 and Th17 cells, play a critical role in the pathologic process of RA. However, it remains unclear how Th1 and Th17 cells are regulated during RA. In this study, we report that the small ubiquitin-like protein X-linked gene in the G6PD cluster at Xq28 (GdX) regulates the balance of Th17 and regulatory T (Treg) cells during collagen-induced arthritis (CIA). We discovered that the splenocytes of GdX-knockout (KO) mice were insensitive to T-cell stimulants. Correspondingly, GdX-KO mice showed alleviative Th1-mediated delayed-type hypersensitivity and were resistant to CIA compared with wild-type mice. GdX-KO mice showed fewer swollen paws, lower serum proinflammatory cytokine and anti-collagen IgG levels, and decreased synovial hyperplasia. Mechanistically, we observed that deletion of GdX decreased the transcription of proinflammatory cytokines and impaired the Th1 and Th17 differentiation but increased the Treg cell proliferation. Consistently, deletion of GdX decreased the transcription level of T-cell-specific T-box transcription factor and RAR-related orphan receptor-γ transcription factor but increased that of forkhead box P3 after being challenged with type-II collagen. These findings suggested that GdX functions as an important regulator of Th1 or Th17 and Treg cell balance during the inflammatory responses. Therefore, GdX may be a potential target for the therapy of RA.-Fu, Y., Liu, S., Wang, Y., Ren, F., Fan, X., Liang, J., Liu, C., Li, J., Ju, Y., Chang, Z. GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of Th1/Th17 and regulatory T cells.
Assuntos
Artrite Experimental/enzimologia , Linfócitos T Reguladores/enzimologia , Células Th1/enzimologia , Células Th17/enzimologia , Ubiquitinas/deficiência , Animais , Artrite Experimental/genética , Artrite Experimental/patologia , Citocinas/genética , Citocinas/metabolismo , Masculino , Camundongos , Camundongos Knockout , Células Th1/patologia , Células Th17/patologia , Transcrição Gênica , Ubiquitinas/metabolismoRESUMO
GdX, also named ubiquitin-like protein 4A, is a ubiquitin-domain protein characterized by a ubiquitin-like domain that regulates the movement of misfolded proteins from the endoplasmic reticulum membrane to proteasome. However, its function in skeletal biology remains unclear. Here, we report that GdX plays a crucial role in skeletal development as mice lacking GdX exhibit skeletal dysplasias, mild kyphosis, and scoliosis. During embryonic stage, GdX knockout mice display decreased bone mineral density and trabecular bone accompanied by delayed osteogenic formation. GdX knockout mice also have blended spine and small body size. At the molecular level, GdX knockout mice showed perturbed expression of osteogenesis-related genes and cartilage developmental genes, indicative of altered differentiation of mesenchymal cell lineage. Collectively, our results uncovered GdX as a novel regulator in bone development and a potential candidate gene for skeletal dysplasias.
Assuntos
Condrogênese , Cifose/metabolismo , Osteoblastos/metabolismo , Osteogênese , Escoliose/metabolismo , Ubiquitinas/metabolismo , Animais , Células Cultivadas , Camundongos Knockout , Ubiquitinas/deficiênciaRESUMO
Mesenchymal stromal cells (MSCs) have been extensively investigated as a potential antiinflammatory treatment in many inflammatory-related diseases; however, it remains unclear whether MSCs could be used to treat acute allergic rhinitis. A rat model of allergic rhinitis was treated with MSCs. The effect of MSCs on the inflammation of allergic rhinitis was evaluated by sneezing, nose rubbing, the pathology of the nasal mucosa, and the expression of interleukin 4, tumour necrosis factor alpha, and immunoglobulin E in the serum of rats. Also, the population of MSCs isolated from umbilical cords of humans was evaluated to determine if they could inhibit the symptoms and inflammation of acute allergic rhinitis in a rat model. We observed that this population of cells inhibited sneezing, nose rubbing, and changes in the pathology of the nasal mucosa. Intriguingly, we observed that MSCs reduced the expression of interleukin 4, tumour necrosis factor alpha, and immunoglobulin E in the serum. Furthermore, MSCs reduced the expression of histamine and the recruitment of macrophages in the nasal mucosa of allergic rhinitis rats. We reasoned that the effect of MSCs on allergic rhinitis might be through its regulation of the secretion of related cytokines from macrophages during the process of acute allergic rhinitis. This work suggested that MSCs from the umbilical cords of humans could be used as a positive clinical therapy for the human disease.
Assuntos
Transplante de Células-Tronco Mesenquimais , Rinite Alérgica/terapia , Doença Aguda , Animais , Células Cultivadas , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Histamina/sangue , Humanos , Imunoglobulina E/sangue , Interleucina-4/sangue , Macrófagos/citologia , Macrófagos/imunologia , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Mucosa Nasal/citologia , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Ratos , Ratos Sprague-Dawley , Rinite Alérgica/metabolismo , Rinite Alérgica/patologia , Transplante Heterólogo , Fator de Necrose Tumoral alfa/sangue , Cordão Umbilical/citologiaRESUMO
BACKGROUND Pediatric sepsis has high morbidity in children, may lead to acute kidney injury (AKI), and further aggravate the disease. Baicalin is a kind of flavonoid in Scutellaria baicalensis Georgi and has been reported to protect against several diseases, but its roles in septic AKI remain unclear. This study aimed to uncover the effects of baicalin in AKI during pediatric sepsis. MATERIAL AND METHODS Blood urea nitrogen (BUN) and serum creatinine (Cr) levels were detected in 50 pediatric patients, who underwent basic therapy with or without baicalin adjunctive therapy. Mouse sepsis models were constructed by cecal ligation and puncture (CLP) and treated with baicalin intragastrically, after which BUN and Cr examination, TUNEL apoptosis assay, and expression analyses of BAX and BCL2 were performed. RESULTS Baicalin adjunctive therapy significantly decreased BUN and Cr levels in pediatric sepsis patients (P<0.05). CLP led to elevated BUN and Cr levels in the mouse model (P<0.01), indicating kidney injury accompanied by sepsis. Baicalin decreased BUN and Cr levels (P<0.05), and reduced the apoptotic cell percent in the renal tissue (P<0.05) of the CLP model. It inhibited BAX and promoted BCL2 in the renal tissue, which was consistent with cell apoptosis changes. CONCLUSIONS Baicalin is capable of suppressing renal cell apoptosis and protecting against AKI in pediatric sepsis. This study provides a potential adjunctive therapy for treating AKI in pediatric sepsis, and further research is necessary to reveal its deeper mechanisms.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Apoptose/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Rim/patologia , Sepse/tratamento farmacológico , Sepse/prevenção & controle , Injúria Renal Aguda/fisiopatologia , Animais , Ceco/patologia , Criança , Pré-Escolar , Modelos Animais de Doenças , Humanos , Lactente , Rim/efeitos dos fármacos , Rim/fisiopatologia , Testes de Função Renal , Ligadura , Masculino , Camundongos Endogâmicos C57BL , Punções , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Pump-jet holds a pivotal position in various marine applications, underscoring the need for comprehending their transient behavior for the purpose of design enhancement and performance refinement. This paper employs Reynolds-averaged Navier-Stokes equations method in conjunction with Detached Eddy Simulation model. The study delves into the ramifications of accelerating and decelerating ducts, distinguished by camber f and attack angles α, on transient hydrodynamic characteristics. The hydrodynamic characteristics are investigated numerically, after the validation of the numerical methodology by comparing simulation outcomes against experimental results. Subsequently, the study delves into propulsion characteristics, followed by an exploration of time-domain and frequency-domain data transformed through fast Fourier transform to analyze thrust fluctuations and pulsating pressures. Additionally, a detailed examination of pressure distribution and velocity field is provided, aiming to dissect the mechanisms through the variations in f and α influence the flow field. Findings suggest that the outlet velocity of accelerating ducts significantly surpasses the inlet velocity, a behavior contrasted by decelerating ducts. Notably, the patterns of accelerating and decelerating ducts resulting from alterations in f exhibit consistent characteristics with those brought about by changes in α. However, several opposite characteristics surface in transient flow field due to the distinct modifications in the duct profile. Furthermore, by considering vorticity magnitude distribution and vortices, a comparative analysis elucidates the effects of varying f and α on rotor and stator trailing vortices. This contributes to understanding the flow instability mechanism under differing duct configurations. It is evident that changes in f and α exert significant influence on both performance and flow field.
RESUMO
Protein post-translational modifications (PTMs) are crucial for cancer cells to adapt to hypoxia; however, the functional significance of lysine crotonylation (Kcr) in hypoxia remains unclear. Herein we report a quantitative proteomics analysis of global crotonylome under normoxia and hypoxia, and demonstrate 128 Kcr site alterations across 101 proteins in MDA-MB231 cells. Specifically, we observe a significant decrease in K131cr, K156cr and K220cr of phosphoglycerate kinase 1 (PGK1) upon hypoxia. Enoyl-CoA hydratase 1 (ECHS1) is upregulated and interacts with PGK1, leading to the downregulation of PGK1 Kcr under hypoxia. Abolishment of PGK1 Kcr promotes glycolysis and suppresses mitochondrial pyruvate metabolism by activating pyruvate dehydrogenase kinase 1 (PDHK1). A low PGK1 K131cr level is correlated with malignancy and poor prognosis of breast cancer. Our findings show that PGK1 Kcr is a signal in coordinating glycolysis and the tricarboxylic acid (TCA) cycle and may serve as a diagnostic indicator for breast cancer.
Assuntos
Neoplasias da Mama , Ciclo do Ácido Cítrico , Glicólise , Fosfoglicerato Quinase , Fosfoglicerato Quinase/metabolismo , Fosfoglicerato Quinase/genética , Humanos , Glicólise/genética , Linhagem Celular Tumoral , Feminino , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Lisina/metabolismo , Processamento de Proteína Pós-Traducional , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Regulação para Baixo , Camundongos , Proteômica/métodos , Camundongos Nus , Regulação Neoplásica da Expressão Gênica , Mitocôndrias/metabolismo , Hipóxia Celular , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/genéticaRESUMO
In this study, an autogenous N-doped biochar derived from Chlorella (CVAC) was prepared with NaOH as activator at 800 °C. The surface structural properties of CVAC and the adsorption performance of CVAC on tetracycline (TC) under different adsorption variables were analyzed and investigated using different characterization methods. The results showed that the specific surface area of CVAC was 491.16 m2 g-1 and the adsorption process was in accordance with Freundlich model and pseudo-second-order kinetic model. The maximum adsorption capacity of TC was 310.696 mg g-1 at pH 9 and 50 °C, and it was mainly physical adsorption. Furthermore, the cyclic adsorption-desorption behavior of CVAC using ethanol as eluent was evaluated and the feasibility of its long-term application was explored. CVAC also showed good cyclic performance. The variation of ΔG° and ΔH° confirmed that the adsorption of TC by CVAC was a spontaneous heat absorption process.
Assuntos
Chlorella , Poluentes Químicos da Água , Adsorção , Porosidade , Tetraciclina/química , Antibacterianos , Carvão Vegetal/química , CinéticaRESUMO
De novo pyrimidine biosynthesis is achieved by cytosolic carbamoyl-phosphate synthetase II, aspartate transcarbamylase and dihydroorotase (CAD) and uridine 5'-monophosphate synthase (UMPS), and mitochondrial dihydroorotate dehydrogenase (DHODH). However, how these enzymes are orchestrated remains enigmatical. Here we show that cytosolic glutamate oxaloacetate transaminase 1 clusters with CAD and UMPS, and this complex then connects with DHODH, which is mediated by the mitochondrial outer membrane protein voltage-dependent anion-selective channel protein 3. Therefore, these proteins form a multi-enzyme complex, named 'pyrimidinosome', involving AMP-activated protein kinase (AMPK) as a regulator. Activated AMPK dissociates from the complex to enhance pyrimidinosome assembly but inactivated UMPS, which promotes DHODH-mediated ferroptosis defence. Meanwhile, cancer cells with lower expression of AMPK are more reliant on pyrimidinosome-mediated UMP biosynthesis and more vulnerable to its inhibition. Our findings reveal the role of pyrimidinosome in regulating pyrimidine flux and ferroptosis, and suggest a pharmaceutical strategy of targeting pyrimidinosome in cancer treatment.
Assuntos
Ferroptose , Neoplasias , Di-Hidro-Orotato Desidrogenase , Proteínas Quinases Ativadas por AMP , Pirimidinas/farmacologia , Proliferação de CélulasRESUMO
AIMS: Human umbilical cord mesenchymal stem cells (HUMSCs) have been documented to be effective for several immune disorders including inflammatory bowel diseases (IBD). However, it remains unclear how HUMSCs function in regulating immune responses and intestinal flora in the trinitrobenzene sulfonic acid (TNBS)-induced IBD model. MATERIALS AND METHODS: We assessed the regulatory effects of HUMSCs on the gut microbiota, T lymphocyte subpopulations and related immune cytokines in the TNBS-induced IBD model. The mice were divided into the normal, TNBS, and HUMSC-treated groups. The effect of HUMSCs was evaluated by Hematoxylin and Eosin (H&E) staining, fluorescence-activated cell sorting (FACS), and enzyme-linked immunosorbent assay (ELISA) analyses. Metagenomics Illumina sequencing was conducted for fecal samples. KEY FINDINGS: We demonstrated that the disease symptoms and pathological changes in the colon tissues of TNBS-induced colitis mice were dramatically ameliorated by HUMSCs, which improved the gut microbiota and rebalanced the immune system, increasing the abundance of healthy bacteria (such as Lactobacillus murinus and Lactobacillus johnsonii), the Firmicutes/Bacteroidetes ratio, and the proportion of Tregs; the Th1/Th17 ratio was decreased. Consistently, the expression levels of IFN-γ and IL-17 were significantly decreased, and transforming growth factor-ß1 (TGF-ß1) levels were significantly increased in the plasma of colitis mice HUMSC injection. SIGNIFICANCE: Our experiment revealed that HUMSCs mitigate acute colitis by regulating the rebalance of Th1/Th17/Treg cells and related cytokines and remodeling the gut microbiota, providing potential future therapeutic targets in IBD.
Assuntos
Colite , Doenças Inflamatórias Intestinais , Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Ácido Trinitrobenzenossulfônico/toxicidade , Colite/induzido quimicamente , Colite/terapia , Citocinas/metabolismo , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/terapia , Linfócitos T Reguladores , Imunidade , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical/metabolismo , Modelos Animais de DoençasRESUMO
Anthurium andraeanum is a tropical flower with high ornamental and economic value. Cold stress is one of the major abiotic stresses affecting the quality and value of A. andraeanum; thus, improving the cold tolerance of this species is an important breeding objective. MicroRNAs (miRNAs) have a critical role in plant abiotic stress responses, but their specific molecular regulatory mechanisms are largely unknown, including those related to the cold stress response in A. andraeanum. Here, we identified and cloned the precursor of miR158 from A. andraeanum (Aa-miR158). Both Aa-miR158 and its target gene (c48247) had higher expression levels in strong leaves than in other tissues or organs. Further study revealed that the transcript level of Aa-miR158 was increased by cold stress. Heterologous overexpression of Aa-miR158 improved cold stress tolerance in Arabidopsis, which was associated with decreases in the malondialdehyde (MDA) concentration and relative electrical conductivity (REC) as well as increases in peroxidase (POD) and catalase (CAT) activity. Moreover, overexpressing Aa-miR158 significantly increased the expression of endogenous genes related to cold stress tolerance and reactive oxygen species (ROS) levels in transgenic Arabidopsis under cold stress. Overall, our results demonstrate that Aa-miR158 is significantly involved in the cold stress response and provide a new strategy for cold tolerance breeding of A. andraeanum.
RESUMO
T helper cells, especially Th1 and Th17 cells, were reported to play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). However, the underlying factors regulating T cell functions in IBD progression remain to be fully elucidated. Here, we revealed that IL-17RD/Sef exacerbates DSS-induced colitis by regulating the balance of T cell subsets and their secretion of associated cytokines. We also observed that IL-17RD/Sef promotes colitis-associated tumorigenesis and negatively correlates with survival in both mouse and colorectal cancer patients. Our results suggested that IL-17RD/Sef functions as a regulator of T cell subsets to promote the inflammatory responses in the pathogenesis of IBD and colitis-associated colon cancer.
Assuntos
Carcinogênese/imunologia , Colite/imunologia , Proteínas de Membrana/imunologia , Células Th1/imunologia , Células Th17/imunologia , Animais , Carcinogênese/genética , Carcinogênese/patologia , Colite/induzido quimicamente , Colite/genética , Colite/mortalidade , Colo/imunologia , Colo/patologia , Sulfato de Dextrana/administração & dosagem , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Inflamação , Interferon gama/genética , Interferon gama/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Contagem de Linfócitos , Masculino , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais , Análise de Sobrevida , Células Th1/patologia , Células Th17/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Exosomes released by mesenchymal stem cells (MSCs) are thought to function as extensions of the MSCs. However, it remains unclear whether exosomes derived from human umbilical cord MSCs (HUMSCs) possess immunoregulatory functions in rheumatoid arthritis. We report that when mice with collagen-induced arthritis were injected with exosomes derived from HUMSC (HUMSC-Exo), their paws became less swollen, and they had lower serum pro-inflammatory cytokine and anti-collagen IgG levels, and decreased synovial hyperplasia. The HUMSC-Exo appeared to restore the balance between Th17 and Treg cells, and this effect was accompanied by reduced IL-17 and enhanced TGF-ß and IL-10 levels. These findings suggest that HUMSC-Exo function as important regulator of the balance between Th1/Th17 and Treg cells during immune and inflammatory responses.
Assuntos
Artrite Experimental , Exossomos , Células-Tronco Mesenquimais , Animais , Humanos , Camundongos , Artrite Experimental/terapia , Citocinas , Imunoglobulina G , Interleucina-10/genética , Interleucina-17 , Linfócitos T Reguladores , Fator de Crescimento Transformador beta , Cordão Umbilical , Células Th17RESUMO
Activated carbon (ENAC) was prepared by NaOH activation, using macroalgae (Enteromorpha clathrate) as raw material. The prepared activated carbon has a large surface area (1238.491 m2 g-1) and its total pore volume and average pore size are 0.6823 cm3g-1 and 2.2038 nm, respectively. The ENAC was characterized by SEM, FTIR, BET and XPS. The effects of contact time (0-960 min), initial tetracycline (TC) concentration (50-500 mg L-1), temperature (30-50 °C) and initial pH (2-11) on TC adsorption were evaluated. The adsorption isotherm and adsorption kinetics were discussed. Results showed that the adsorption isotherm was the Langmuir model, and the adsorption process can be described by the pseudo-second-order model. The N2 adsorption-desorption isotherm was type IV, indicating that the activated carbon had mesoporous structure. Thermodynamic analysis showed that the adsorption process was endothermic and spontaneous. The maximum adsorption capacity of TC was 381.584 mg g-1. Density functional theory (DFT) was used to simulate and analyze the adsorption process, and the influence of different types of N on the adsorption was expounded. The results showed that there are electrostatic interactions, π-π interactions and hydrogen bonding between the adsorbent and TC. These results indicated that the prepared ENAC had a great application prospect in the removal of antibiotics from aqueous solution.
Assuntos
Alga Marinha , Poluentes Químicos da Água , Adsorção , Antibacterianos , Carvão Vegetal , Concentração de Íons de Hidrogênio , Cinética , Hidróxido de Sódio , Tetraciclina , TermodinâmicaRESUMO
Mesenchymal stem cells (MSCs) have been documented to be effective for the therapy of inflammation-related diseases but raised concerns on possible tumorigenic effects. Since most of the tumors are induced or promoted by chronic inflammation, one could expect that MSCs might be beneficial for the cancer therapy because of their potent roles on inhibiting inflammation. This study is aimed at performing a safety evaluation and evaluating the role of human umbilical cord mesenchymal stem cells (HUC-MSCs) on tumorigenesis. We found that HUC-MSCs cultured within 20 generations had no significant changes in proliferation, cell cycle, cellular senescence, apoptosis, and expression of mesenchymal stem cell markers. HUC-MSCs were unable to form any tumor in immunodeficiency or normal mice with or without inflammatory stimulation. Intriguingly, we observed that HUC-MSCs inhibited tumorigenesis in B16-derived or AOM/DSS-induced colon cancer models. We reasoned that the effect of HUC-MSCs on tumorigenesis might be through regulating the inflammatory response. Indeed, HUC-MSCs dramatically ameliorated the disease symptoms and pathological changes of DSS-induced colitis mice. We deciphered the mechanism that HUC-MSCs inhibited tumorigenesis through reducing the proportion of macrophages, which were decreased in the mice suffered from AOM/DSS-induced colon cancer. Correspondingly, the expression levels of TNF-α and IL-6, which were secreted by macrophages, were significantly decreased in the plasma of colon cancer and colitis mice after injection of HUC-MSCs. This study revealed the role of inhibiting macrophages and shed light on the therapeutic application of HUC-MSCs in inflammation-induced tumorigenesis.
RESUMO
Rheumatoid arthritis (RA) is exacerbated by TNF-alpha signaling. However, it remains unclear whether TNF-α-activated TNFR1 and TNFR2 are regulated by extracellular factors. Here, we showed that soluble glycosylated interleukin-17 receptor D (sIL-17RD), which was produced by proteolytic cleavage, enhanced TNF-α-induced RA. We revealed that IL-17RD shedding was induced by the proteolytic enzyme TACE and enhanced by TNF-α expression in macrophages. Intriguingly, sIL-17RD was elevated in the sera of arthritic mice and rats. Recombinant sIL-17RD significantly enhanced the TNF-α-induced proinflammatory response by promoting TNF-α-TNFR-sIL-17RD complex formation and receptor clustering, leading to the accelerated development of collagen-induced arthritis. Our observations revealed that ectodomain shedding of IL-17RD occurred in RA to boost the TNF-α-induced inflammatory response. Targeting sIL-17RD may provide a new strategy for the therapy of RA.
Assuntos
Artrite Experimental , Artrite Reumatoide , Receptores de Interleucina-17 , Receptores do Fator de Necrose Tumoral/metabolismo , Animais , Artrite Reumatoide/metabolismo , Análise por Conglomerados , Camundongos , Ratos , Receptores de Interleucina-17/sangue , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Anesthetics are thought to be involved in immunomodulation. Avertin is one of the safest and most commonly used intravenous anesthetics in rodent experiments; it is also widely used in euthanasia of inflammatory bowel disease (IBD) models. This study aimed to define the role and mechanism of action of Avertin on murine colitis. We assessed the effects of a single Avertin injection on colitis using the disease activity index (DAI), pathology, enzyme-linked immunosorbent assay (ELISA), multiplex-ELISA, flow cytometry, and routine blood examination in wild-type (WT) and dextran sodium sulphate (DSS)-treated mice. Although Avertin caused acute cecitis in WT mice after 24 h and aggravated inflammation in the medium term, it alleviated inflammation in the late stage of DSS-induced colitis according to the DAI. Avertin upregulated MPO production and induced the accumulation of neutrophils and macrophages in intestinal mucosa of both WT and DSS-treated mice; the altered MPO might indicate a change in respiratory burst. However, it exhibited a more effective suppression of inflammatory factors secreted by macrophages as the colitis progressed. Avertin led to an increase in neutrophils and decrease in monocytes in both WT and DSS-treated mice blood. Our findings suggest that Avertin aggravates inflammation in the early and medium terms, but alleviates inflammation in the late stage of colitis by regulating neutrophils and macrophages.
Assuntos
Anestésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Etanol/análogos & derivados , Macrófagos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Animais , Ceco/efeitos dos fármacos , Ceco/patologia , Colite/induzido quimicamente , Colite/imunologia , Colite/patologia , Colo/efeitos dos fármacos , Colo/imunologia , Sulfato de Dextrana , Etanol/uso terapêutico , Feminino , Contagem de Leucócitos , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos C57BL , Neutrófilos/imunologiaRESUMO
Anthurium andraeanum Lind. is a popular potted and cut-flower plant with an attractive spathe and foliage. It is native to tropical rainforest areas and is able to blossom throughout the year under suitable conditions. However, various abiotic stresses seriously restrict the ornamental value of A. andraeanum and increase the costs of cultivation. A dark green (dg) leaf color mutant of A. andraeanum 'Sonate', which accumulates high levels of anthocyanin, has shown increased vigor and tolerance to stresses during cultivation and is, thus, an ideal germplasm for studying stress tolerance in this species. Here, we show that the anthocyanin content in dg mutant plants at different stages of leaf development was higher than in wild-type (WT) plants, and the ability to tolerate under low-temperature (LT, 14 °C) stress was stronger in dg than in WT plants. RNA-Seq of cDNA libraries from young leaves of dg and WT identified AabHLH35 as a differentially expressed gene (DEG) that was significantly up-regulated in dg. Furthermore, heterologous expression of AabHLH35 improved tolerance to cold and drought stresses in Arabidopsis. These results have built an important molecular foundation for further study of stress tolerance in A. andraeanum.